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The young Robert Tattersall was working on a study of long term diabetes at King’s College London, when he came across a woman with a 40 year history of diabetes who had stopped taking insulin. So too had some of her relatives. David Pyke—Robert’s mentor—recalled the same phenomenon in another family. This simple clinical observation and some intensive sleuth work led to the discovery of maturity onset diabetes of the young (MODY), the first single gene variant of diabetes to be described. It opened up a whole new field of research, which continues to yield a dividend both for science and for those who carry the genes involved. Robert was born to two psychiatrists and went on to marry one. This, he said, “may go some way to explaining my interest in the psychological aspects of diabetes and the hinterland between medicine and psychiatry.” He studied at Cambridge and St Thomas’ Hospital and did a senior house officer job at Nottingham General Hospital before joining David Pyke in London. It was an exciting time to be in diabetes. The genetic heterogeneity of the condition was coming to …

Cancer is an increasing cause of morbidity and mortality in most countries. It has recently overtaken heart disease as the commonest cause of death in the United Kingdom. “Breakthroughs” in cancer research are reported regularly in the media. Some reports are based on new results that show potential for improved treatments, but others are premature or publicity seeking, and the motivation behind them is questionable. The public has high expectations that basic science cancer research will translate into improved cancer cures and care. Yet awareness and understanding of the clinical trials that are essential in establishing the effectiveness of new treatments is limited. Recruitment to randomised clinical trials evaluating new cancer treatments is often slow, partly because people are convinced that all new treatments are likely to be an improvement and partly because of unease about the process of randomisation. Better public education about categories of evidence in relation to health interventions might contribute to speedier and more appropriate evaluation of promising treatments. Public confidence that cancer care in the United Kingdom is optimal has been shaken by reports that outcomes for some common cancers differ in countries in western Europe, and that survival rates in Britain for 18 of 25 cancer types studied are poorer than in most other European countries.1,2 Better than average outcomes were seen in Switzerland, Finland, and Holland. These reports, together with evidence that cancer survival rates differ within a country according to the pattern of care, prompted review of the provision of care for cancer patients in the United Kingdom and in parts of Australia.3–6 Optimal organisation of cancer care might achieve appreciable gains. In the case of breast cancer, this could amount to a 5% improvement in the survival rate at five years. Such a gain would be viewed as a major breakthrough if it were the result of a new treatment. In this article we discuss five important recent advances in oncology. Four advances are related to the organisation of care, and are as important, in terms of a deliverable improved outcome, as any recent research findings or new treatments. These four advances are: the multidisciplinary cancer treatment team; supportive care for cancer patients; definition of treatment goals; and the status of clinical trials. In addition, we discuss the exciting treatment advances in areas other than radiation therapy and cytotoxic chemotherapy. Recent advances Multidisciplinary treatment teams specialising in specific organ sites have been recognised as being important for optimal cancer care and for improving outcome The organisation and delivery of supportive care to patients with cancer has improved Treatment goals are more clearly defined Public awareness and understanding of the clinical trials that are driving clinical research has increased Research has started on potential treatments such as matrix metalloproteinase inhibitors, gene therapy, and cancer vaccines

The National Diabetes Data Group's definition of insulin dependent diabetes misleadingly talks of “predominant onset in youth.”1 Over 40 years ago Lawrence wrote that many diabetic patients aged over 70 were insulin deficient.2 It has recently been shown in Denmark that the annual incidence of insulin dependent diabetes after the age of 30 is 8.2 per 100 000 and is remarkably constant from the fourth to the ninth decade; thus at least 44% of all cases are diagnosed after the age of 30.3 We report on two patients who developed insulin dependent diabetes at the ages of 88 and 93. ### CASE 1 An 88 year old woman presented with a five month history of lethargy, weight loss, and nocturia. She was found to be hypothyroid, with a high titre of thyroid autoantibodies. One of her seven siblings had developed diabetes of uncertain type at the age of 75 and a granddaughter had Graves' disease. A month later she became thirsty, was found to have diabetes, and was treated with glibenclamide 5 mg twice daily by her general practitioner. She was referred to us three months later with a random blood glucose concentration of 15.1 mmol/l and a haemoglobin A1 concentration of 11.6% (normal range 5.0%-7.5%). Apart from bilateral cataracts there were no diabetic complications, but she had a body mass index of 23 kg/m2 and was …

Angela Coulter, Vikki Entwistle, David Gilbert King's Fund, £16.95, pp 216 ISBN 1857172140 ![][1] Rating: ![Graphic][2] ![Graphic][3] ![Graphic][4] ![Graphic][5] Pamphlets and, recently, audiotapes and videos have become a usual, visible, and promoted source of information for patients in general practice, in specialist consulting rooms, and in outpatient clinics. These information aids have been produced by a wide range of organisations in response to increasing patient expectations for factual or experiential information about investigations, illness and its causes, treatment options, support services, and likely outcomes. The quality, availability, acceptability, and effectiveness of information sources developed by authoritative bodies is commonly assumed. Many clinicians … [1]: /embed/graphic-1.gif [2]: /embed/inline-graphic-1.gif [3]: /embed/inline-graphic-2.gif [4]: /embed/inline-graphic-3.gif [5]: /embed/inline-graphic-4.gif

G Walker, J Bradburn, J Maher / King's Fund, £6.95, pp 50 / ISBN 1 85717 135 7 This book is the fourth publication in the Promoting Patient Choice series in the clinical change programme supported by the King's Fund. The book describes a process for gaining consensus from health professionals, patient support groups, and patients about how doctors communicate the diagnosis of cancer to patients. The views of 27 consultants who frequently disclose diagnoses of cancer were sought in individual interviews lasting an average of 45 minutes. The views of patients about the …

Dietary non-compliance is an important cause of poor metabolic control in insulin dependent diabetes. Patients are often blamed, but teaching methods may be at fault, so a prospective study was set up to compare the effect of three different teaching methods. After a three month run in, 40 adults with longstanding poorly controlled insulin dependent diabetes (mean haemoglobin A1 13.0%) were allocated at random to three teaching methods: conventional diet sheet instruction (group 1); practical lunchtime demonstrations (group 2); videotape education (group 3). Knowledge was assessed by questionnaires, compliance by seven day food records, and glycaemic control by serial glycosylated haemoglobin measurements. During six months of follow up there was no improvement in knowledge, compliance, or HbA1 in group 1, but in groups 2 and 3 both knowledge and compliance improved. In group 2 HbA1 fell to 10.6 (SD 2.1)% and in group 3 to 9.6 (2.3)%. The change in HbA1 showed an appreciable correlation with dietary compliance as judged by day to day consistency in carbohydrate intake. These findings show that new and interesting educational methods can have a major influence on knowledge, compliance, and metabolic control in insulin dependent diabetes.

OBJECTIVE--To compare high fibre diet, basal insulin supplements and a regimen of insulin four times daily in non-insulin dependent (type II) diabetic patients who were poorly controlled with sulphonylureas. DESIGN--Run in period lasting 2-3 months during which self monitoring of glucose concentration was taught, followed by six months on a high fibre diet, followed by six months' treatment with insulin in those patients who did not respond to the high fibre diet. SETTING--Teaching hospital diabetic clinics. PATIENTS--33 patients who had had diabetes for at least two years and had haemoglobin A1 concentrations over 10% despite receiving nearly maximum doses of oral hypoglycaemic agents. No absolute indications for treatment with insulin. INTERVENTIONS--During the high fibre diet daily fibre intake was increased by a mean of 16 g (95% confidence interval 12 to 20 g.) Twenty five patients were then started on once daily insulin. After three months 14 patients were started on four injections of insulin daily. ENDPOINT--Control of diabetes (haemoglobin A1 concentration less than or equal to 10% and fasting plasma glucose concentration less than or equal to 6 mmol/l) or completion of six months on insulin treatment. MEASUREMENTS AND MAIN RESULTS-- No change in weight, diet, or concentrations of fasting glucose or haemoglobin A1 occurred during run in period. During high fibre diet there were no changes in haemoglobin A1 concentrations, but mean fasting glucose concentrations rose by 1.7 mmol/l (95% confidence interval 0.9 to 2.5, p less than 0.01). With once daily insulin mean concentrations of fasting plasma glucose fell from 12.6 to 7.6 mmol/l (p less than 0.001) and haemoglobin A1 from 14.6% to 11.2% (p less than 0.001). With insulin four times daily concentrations of haemoglobin A1 fell from 11.5% to 9.6% (p less than 0.02). Lipid concentrations were unchanged by high fibre diet. In patients receiving insulin the mean cholesterol concentrations fell from 7.1 to 6.4 mmol/l (p less than 0.0001), high density lipoprotein concentrations rose from 1.1 to 1.29 mmol/l (p less than 0.01), and triglyceride concentrations fell from 2.67 to 1.86 mmol/l (p less than 0.05). Patients taking insulin gained weight and those taking it four times daily gained an average of 4.2 kg. CONCLUSIONS--High fibre diets worsen control of diabetes in patients who are poorly controlled with oral hypoglycaemic agents. Maximum improvements in control of diabetes were achieved by taking insulin four times daily.

Although patients taking phenformin are more likely to develop lactic acidosis in the presence of renal, cardiovascular, or hepatic disease, criteria for safe use of the drug are not well established. Eight diabetics died of lactic acidosis in Nottingham in 1972-5 and all were taking phenformin in therapeutic doses. Six had attended the diabetic clinic within a month of their terminal illness. Two patients had appreciable renal impairment and should not have been given phenformin. Four had hypertension and minimal evidence of renal disease, while in two no predisposing factor was identified. There are so many contraindications to the use of phenformin that it is doubtful whether patients on the drug can be monitored adequately. We suggest that phenformin should be withdrawn from general use.

Skin biopsy samples from 14 diabetic patients with lipoatrophy at injection sites and from five insulin-treated diabetic patients without such lipoatrophy (controls) were examined by immunofluorescence for the deposition of immunological components. Also sera from 13 of the patients with lipoatrophy and from all of the controls were assayed for insulin-binding capacity. Biopsy samples from the edge of lipoatrophic areas (eight cases) invariably showed abnormal deposition of immunological components in dermal vessel walls, whereas no such deposition was seen in the control samples. Mean serum insulin-binding capacity was 33.1 microgram/l in the patients with lipoatrophy compared with only 4.6 microgram/l in the controls. These findings suggest that insulin-induced lipoatrophy results from the local formation of immune complexes, complement fixation, and release of inflammatory mediators from the cellular infiltrate.

In one year a prospective survey in a large accident and emergency department identified 204 admissions of adults with severe hypoglycaemia, 200 in insulin-treated patients. Ninety-six had one admission while 34 others were admitted on 104 occasions. Of the 130 patients, 111 attended diabetic clinics in Nottingham, forming 9% of a known clinic population of 1229 on insulin treatment. Since many other episodes of hypoglycaemia were presumably treated outside hospital, 9% a year is a minimum estimate of the incidence of severe hypoglycaemia in our area. The mean insulin dose was 1.2 units/kilogram/day for those admitted twice or more and 0.9 U/kg/day for those admitted once; these doses were significantly higher than those of an age-matched clinic population. A year after the latest admission with hypoglycaemia, the mean insulin dose in the group with two or more admissions had fallen to 0.8 U/kg/day, suggesting that over-treatment had been an important causal factor. A similarly high incidence has been reported in other studies, and we believe that it is due mainly to the inadequacy of conventional subcutaneous insulin treatment.

Seventy-two patients with advanced squamous-cell carcinomas of the head and neck were randomised to receive weekly intravenous methotrexate at doses of either 50 mg/m2 (low dose), 500 mg/m2 (medium dose), or 5 g/m2 (high dose). Patients who failed to respond after four treatments at their initial dose were given four further treatments at the next higher dose. There were two complete responses and 21 partial responses to the initial dose--in 10 out of 22 patients given the high dose, seven out of 27 given the medium dose, six out of 23 given the low dose. A further five out of 16 patients responded after crossing over to a higher dose. Toxicity was more severe with the high-dose regimen. Responders survived significantly longer than non-responders (p less than 0.05), but there was no significant difference in durations of survival among the three treatment groups. Analysis of patients who completed the first four treatments indicated an improved response rate and duration of survival for the high-dose group. Because of toxicity associated with high-dose methotrexate this treatment produces no overall greater benefit than low-dose regimens.